This K01 proposal entitled "Moving Toward Independence: Exploring neurological and endocrine determinants of adolescent and young adult risky behavior decision-making" in response to the program announcement (PA-09-040) proposes a rigorous mixed methods approach to examine how adolescents and young adults (ages 18-24) make decisions about engaging in risky behaviors. This one-year longitudinal study, the first of its kind, incorporates fMRI, salivary samples, genital swabs, and ACASI (Audio Computer Assisted Self-Interview) and in-the-moment text messaging survey methods into one project to examine neurological, hormonal, psychological, and contextual determinants of sexual risk practices and substance use and their related outcomes (e.g., HIV, STIs, substance use disorders, drug dependency, depression). The objective and specific aims of this study are listed below: Objective: The research questions motivating the proposed study are: Why do young adults engage in risky behaviors (sexual and substance use) when they are knowledgeable about consequences? To what extent do these youth experience feelings of depressive symptoms, heightened stress, and physical consequences (e.g., STIs, HIV, drug use disorders)? How do relationships between determinants of risk and outcomes change over time? Aim 1: Assess, using fMRI whether cognitive control brain regions of interest (CCROIs: prefrontal cortex pruning and parietal association cortex;dorsolateral prefrontal cortex;ventromedial prefrontal cortex;anterior and posterior cingulate, and temporo-parietal cortices) and socio-emotional brain regions of interest (SEROIs: medial frontal cortex, left ventral striatum - in the accumbens, left superior temporal sulcus, left medial tempor- al, amygdala) are differentially active in youths who take fewer sexual and substance use risks relative to youths taking greater risks. Aim 2: Assess, via four salivary measures per day, whether testosterone (T) and dehydroepiandrosterone (DHEA) levels and diurnal patterns vary as a function of the cognitive control and socio-emotional network brain region activity and development for young women and men. Aim 3: Investigate how activation in cognitive control relative to socio-economic brain networks relates to youths'reports of (a) mental health outcomes and (b) physical health outcomes. By extension, assess how hormone and brain region patterns (e.g., high T with low cognitive control) relate to youths'reports of sexual risk, substance use, drug abuse and dependency, and mental health. Aim 4: Assess changes in brain function as well as hormone diurnal changes over one year's development and whether these changes are related to (1) each other and (2) changes/ stability in sexual risk behavior and substance use outcomes as well as mental health outcomes. At the completion of this project, as a young investigator I will (1) learn the fundamentals of neuroscience and endocrinology, sufficient to launch my independent career, and (2) have a better understanding of how hormones, brain region activity, and context influence a young person's risky behaviors and how these hormones and brain ROI relate to risky behaviors and mental health outcomes over time. This work will advance the current knowledge of adolescent and young adult decision-making and mental health and behavioral outcomes by creating and assessing a more comprehensive model via integrating psychological, biological, and contextual perspectives, and will serve as the basis for an R01 application and future analyses beyond the scope of this study. PUBLIC HEALTH RELEVANCE: Moving Toward Independence: Exploring neurological and endocrine determinants of adolescent and young adult risky behavior decision-making Project Narrative The candidate's immediate training and research agenda is to develop an improved and comprehensive understanding - using biological and survey measures - of how adolescents and young adults make decisions to engage in risky behaviors. The proposed 1-year longitudinal study focuses on understanding risky sexual practice and substance use decision making and related outcomes (e.g., HIV, STIs, substance use disorders, drug dependency, depression) from neuroscience and endocrinology perspectives, disciplines in which the candidate seeks training. This research agenda has major policy and prevention implications for adolescent and young adult well-being.